Chapter 21 Lipids as second messengers

Normal physiology demands that various cell types in the human body interact productively with other cell types and respond to various stimuli from their environment. These stimuli instruct the target cell types to perform specific functions such as hormone release, granule secretion, modulation of intermediary metabolism, reaction to infections and tissue injury, cell division and multiplication, cell differentiation, or cell death. These instructions are translated within the target cell types through the process of signal transduction which involves a number of biochemical reactions that are turned on by the extracellular stimuli, and in turn lead to modification of cell function (see Figure 3 for an example on platelet function). Membrane lipids have emerged as key components in this signal transduction pathway with products of lipid metabolism serving as important second messengers that are generated in response to extracellular stimuli. These lipid second messengers interact with specific biochemical targets such as protein kinases and phosphatases, as well as with metabolic enzymes, thus launching a cascade of intracellular changes. Diacylglycerol is the best studied and documented lipid second messenger. Its levels are increased transiently in response to a number of growth factors and hormones. This elevation in diacylglycerol levels results in activation of the protein kinase C family of enzymes which serve as switches in regulation of cell function through the phosphorylation of a number of cellular protein substrates. Other lipids and lipid-derived molecules also are emerging as potential second messengers. Derangements in these signal transduction pathways involving lipid precursors, lipid-metabolizing enzymes, lipid second messengers, and targets of lipid second messengers may underlie diverse pathologic conditions including cancer, autoimmune disorders, inflammatory conditions, and cell senescence and cell death.